2-(5-methoxy-1H-benzimidazol-2-yl)phenol | 939752-51-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(5-methoxy-1H-benzimidazol-2-yl)phenol
• 英文别名: 2-(6-methoxy-1H-benzimidazol-2-yl)phenol
• CAS: 939752-51-9
• 化学式: C₁₄H₁₂N₂O₂
• mdl: MFCD09699743
• 分子量: 240.261
• InChiKey: SFCFWPHAMYMCPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  58.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(5-methoxy-1H-benzimidazol-2-yl)phenol 在 氢溴酸 、 溶剂黄146 作用下， 反应 24.0h， 生成 5(6)-Hydroxy-2-(2-hydroxy-phenyl)-benzimidazol
  参考文献：
  名称：

  Synthesis, antioxidant, and antimicrobial evaluation of some 2-arylbenzimidazole derivatives

  摘要：

  A series of 2-arylbenzimidazole derivatives (3a-3p and 4a-4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO center dot) scavenging, superoxide radical anion (O-2(center dot)) scavenging, 1,1-diphenyl- 2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO center dot scavenging activity (EC50 = 46 mu M) in vitro had a significant reduction of 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H2O2-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.004
• 作为产物：
  描述：

  水杨醛 、 2-硝基-4-甲氧基苯胺 在 sodium dithionite 作用下， 以 甲醇 为溶剂， 反应 0.6h， 生成 2-(5-methoxy-1H-benzimidazol-2-yl)phenol
  参考文献：
  名称：

  Synthesis, antioxidant, and antimicrobial evaluation of some 2-arylbenzimidazole derivatives

  摘要：

  A series of 2-arylbenzimidazole derivatives (3a-3p and 4a-4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO center dot) scavenging, superoxide radical anion (O-2(center dot)) scavenging, 1,1-diphenyl- 2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO center dot scavenging activity (EC50 = 46 mu M) in vitro had a significant reduction of 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H2O2-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.004

文献信息

• Cancer therapeutics
  申请人：UNIVERSITY OF VIRGINIA PATENT FOUNDATION

  公开号：US10562890B2

  公开（公告）日：2020-02-18

  This invention relates to compounds that bind to wild-type CBFβ and inhibit CBFβ binding to RUNX proteins. The potent compounds of the invention inhibit this protein-protein interaction at low micromolar concentrations, using allosteric mechanism to achieve inhibition, displace wild-type CBFβ from RUNX1 in cells, change occupancy of RUNX1 on target genes, and alter gene expression of RUNX1 target genes. These inhibitors show clear biological effects consistent with on-target RUNX protein activity. Pharmaceutical compositions containing a compound of the invention and a pharmaceutically acceptable carrier represent a separate embodiment of the invention. Another embodiment of the invention are methods of treating a RUNX-signaling-dependent cancer that expresses wild-type CBFβ in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention. In one embodiment, the cancer is selected from the group consisting of a RUNX-signaling-dependent leukemia that expresses wild-type CBFβ, lung cancer, bladder cancer, ovarian cancer, uterine cancer, endometrial cancer, breast cancer, liver cancer, pancreatic cancer, stomach cancer, cervical cancer, lymphoma, leukemia, acute myeloid leukemia, acute lymphocytic leukemia, salivary gland cancer, bone cancer, brain cancer, colon cancer, rectal cancer, colorectal cancer, kidney cancer, skin cancer, melanoma, squamous cell carcinoma of the tongue, pleomorphic adenoma, hepatocellular carcinoma, pancreatic cancer, squamous cell carcinoma, and/or adenocarcinoma. In another embodiment, the compounds of the invention can be used to treat a leukemia, lung cancer, ovarian cancer, and/or breast cancer.

  本发明涉及与野生型 CBFβ 结合并抑制 CBFβ 与 RUNX 蛋白结合的化合物。本发明的强效化合物可在低微摩尔浓度下抑制这种蛋白-蛋白相互作用，利用异构机制实现抑制作用，将细胞中的野生型 CBFβ 从 RUNX1 中置换出来，改变 RUNX1 对靶基因的占有率，并改变 RUNX1 靶基因的基因表达。这些抑制剂显示出与靶上 RUNX 蛋白活性一致的明显生物效应。含有本发明化合物和药学上可接受的载体的药物组合物代表了本发明的另一个实施方案。本发明的另一个实施方案是通过向有需要的受试者施用治疗有效量的本发明化合物来治疗表达野生型 CBFβ 的 RUNX 信号依赖性癌症的方法。在一个实施方案中，所述癌症选自由表达野生型 CBFβ 的 RUNX 信号依赖性白血病、肺癌、膀胱癌、卵巢癌、子宫癌、子宫内膜癌、乳腺癌、肝癌、胰腺癌、胃癌、宫颈癌、淋巴瘤、白血病、急性髓性白血病、急性淋巴细胞白血病、急性淋巴细胞白血病、急性髓细胞白血病、急性淋巴细胞白血病、唾液腺癌、骨癌、脑癌、结肠癌、直肠癌、结直肠癌、肾癌、皮肤癌、黑色素瘤、舌鳞癌、多形性腺瘤、肝细胞癌、胰腺癌、鳞状细胞癌和/或腺癌。在另一个实施方案中，本发明的化合物可用于治疗白血病、肺癌、卵巢癌和/或乳腺癌。
• CANCER THERAPEUTICS
  申请人：University Of Virginia Patent Foundation

  公开号：EP3180004B1

  公开（公告）日：2021-01-06
• Synthesis, antioxidant, and antimicrobial evaluation of some 2-arylbenzimidazole derivatives
  作者：Binhua Zhou、Baojian Li、Wei Yi、Xianzhang Bu、Lin Ma

  DOI：10.1016/j.bmcl.2013.05.004

  日期：2013.7

  A series of 2-arylbenzimidazole derivatives (3a-3p and 4a-4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO center dot) scavenging, superoxide radical anion (O-2(center dot)) scavenging, 1,1-diphenyl- 2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO center dot scavenging activity (EC50 = 46 mu M) in vitro had a significant reduction of 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H2O2-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations. (C) 2013 Elsevier Ltd. All rights reserved.